Myriocin, also known as antibiotic ISP-1 and thermozymocidin, is a
non-proteinogenic amino acid
In biochemistry, non-coded or non-proteinogenic amino acids are distinct from the 22 proteinogenic amino acids (21 in eukaryotesplus formylmethionine in eukaryotes with prokaryote organelles like mitochondria) which are naturally encoded in the ...
derived from certain
thermophilic
A thermophile is an organism—a type of extremophile—that thrives at relatively high temperatures, between . Many thermophiles are archaea, though they can be bacteria or fungi. Thermophilic eubacteria are suggested to have been among the ear ...
fungi.
Myriocin is a very potent inhibitor of
serine palmitoyltransferase
In enzymology, a serine C-palmitoyltransferase () is an enzyme that catalyzes the chemical reaction:
:palmitoyl-CoA + L-serine \rightleftharpoons CoA + 3-dehydro-D-sphinganine + CO2
Thus, the two substrates of this enzyme are palmitoyl-CoA ...
, the first step in
sphingosine
Sphingosine (2-amino-4-trans-octadecene-1,3-diol) is an 18-carbon amino alcohol with an unsaturated hydrocarbon chain, which forms a primary part of sphingolipids, a class of cell membrane lipids that include sphingomyelin, an important phospholip ...
biosynthesis.
Due to this property, it is used in biochemical research as a tool for depleting cells of
sphingolipid
Sphingolipids are a class of lipids containing a backbone of sphingoid bases, a set of aliphatic amino alcohols that includes sphingosine. They were discovered in brain extracts in the 1870s and were named after the mythological sphinx beca ...
s.
Myriocin was shown to inhibit the proliferation of an
IL-2
The Ilyushin Il-2 (Russian: Илью́шин Ил-2) is a ground-attack plane that was produced by the Soviet Union in large numbers during the Second World War. The word ''shturmovík'' (Cyrillic: штурмовик), the generic Russian term ...
-dependent mouse cytotoxic
T cell
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell ...
line.
Myriocin possesses
immunosuppressant
Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system.
Classification
Immunosuppressive drugs can be classified into ...
activity. It is reported to be 10- to 100-fold more potent than
ciclosporin
Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's diseas ...
.
The
multiple sclerosis drug
fingolimod
Fingolimod, sold under the brand name Gilenya, is an immunomodulating medication, mostly used for treating multiple sclerosis (MS). Fingolimod is a sphingosine-1-phosphate receptor modulator, which sequesters lymphocytes in lymph nodes, preve ...
was derived from myriocin by using
structure–activity relationship The structure–activity relationship (SAR) is the relationship between the chemical structure of a molecule and its biological activity. This idea was first presented by Crum-Brown and Fraser in 1865.
The analysis of SAR enables the determination o ...
studies to determine the parts of the molecule important to its activity.
References
{{Lysophospholipid signaling
Antibiotics
Amino acids
Beta hydroxy acids
Vicinal diols